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Choosing a Skeletal Muscle Relaxant Sharon See, Pharmd, BCPS, and Regina Ginzburg, Pharmd St

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Choosing a Skeletal Muscle Relaxant Sharon See, Pharmd, BCPS, and Regina Ginzburg, Pharmd St Choosing a Skeletal Muscle Relaxant SHARON SEE, PharmD, BCPS, and rEGINA gINZBURG, PharmD St. John’s University College of Pharmacy and Allied Health Professions, Jamaica, New York Skeletal muscle relaxants are widely used in treating musculoskeletal conditions. However, evidence of their effectiveness consists mainly of studies with poor methodologic design. In addition, these drugs have not been proven to be superior to acetaminophen or nonsteroidal anti-inflammatory drugs for low back pain. Systematic reviews and meta-analyses support using skeletal muscle relaxants for short-term relief of acute low back pain when nonsteroidal anti-inflammatory drugs or acetaminophen are not effective or tolerated. Comparison studies have not shown one skeletal muscle relaxant to be superior to another. Cyclobenzaprine is the most heavily studied and has been shown to be effective for various musculoskeletal conditions. The sedative properties of tizanidine and cyclobenzaprine may benefit patients with insomnia caused by severe muscle spasms. Methocarbamol and metaxalone are less sedating, although effectiveness evidence is limited. Adverse effects, particularly dizziness and drowsiness, are consistently reported with all skeletal muscle relaxants. The potential adverse effects should be communicated clearly to the patient. Because of limited comparable effectiveness data, choice of agent should be based on side-effect profile, patient preference, abuse potential, and possible drug interactions. (Am Fam Physician. 2008;78(3):365-370. Copyright © 2008 American Acad- emy of Family Physicians.) keletal muscle relaxants are often conditions. The American Pain Society and prescribed for musculoskeletal con- the American College of Physicians recom- ditions including low back pain, neck mend using acetaminophen and nonsteroi- pain, fibromyalgia, tension head- dal anti-inflammatory drugs (NSAIDs) as S aches, and myofascial pain syndrome. The first-line agents for acute low back pain and goals of treatment include managing muscle reserving skeletal muscle relaxants as an pain and improving functional status so the alternative treatment option.12 This recom- patient can return to work or resume previ- mendation is based on available literature, ous activities. which shows skeletal muscle relaxants are Skeletal muscle relaxants are divided into better than placebo, but not more effective two categories: antispastic (for conditions than NSAIDs in patients with acute back such as cerebral palsy and multiple sclero- pain. Similar recommendations exist in sis) and antispasmodic agents (for muscu- treating tension headaches.13 A meta-analysis loskeletal conditions). Antispastic agents evaluating the use of cyclobenzaprine showed (e.g., baclofen [Lioresal], dantrolene [Dant- that, although this drug was better than pla- rium]) should not be prescribed for muscu- cebo for the treatment of fibromyalgia, it loskeletal conditions because there is sparse was considered inferior to antidepressants.14 evidence to support their use. Rather, an Additionally, recent guidelines on fibromy- antispasmodic agent may be more appropri- algia recommend using a comprehensive ate (Table 1).1-9 approach that utilizes tramadol (Ultram), Among antispasmodic agents, cariso- antidepressants, and/or a heated pool (with prodol (Soma), cyclobenzaprine (Flexeril), or without exercise).15 metaxalone (Skelaxin), and methocarba- Prescription rates for nonspecific back mol (Robaxin) were among the top 200 pain revealed that skeletal muscle relaxants drugs dispensed in the United States in accounted for 18.5 percent of prescriptions 2006.10,11 Despite their popularity, skeletal compared with 16.3 percent for NSAIDs and muscle relaxants should not be the primary 10 percent for cyclooxygenase-2 inhibitors.16 drug class of choice for musculoskeletal Because of the high rate of prescribing skeletal Downloaded from the American Family Physician Web site at www.aafp.org/afp. Copyright © 2008 American Academy of Family Physicians. For the private, noncommercial use of one individual user of the Web site. All other rights reserved. Contact [email protected] for copyright questions and/or permission requests. Skeletal Muscle Relaxants Table 1. Skeletal Muscle Relaxants (Antispasmodic Agents) Drug Recommended dosage Most common adverse effects Comments Monthly cost* Carisoprodol 350 mg four times daily Dizziness, drowsiness, headache Physical or psychological dependence may occur; withdrawal symptoms may occur with $72 to $100 (generic) (Soma)1 Not recommended for children Rare idiosyncratic reactions (mental status changes, transient discontinuation $590 (brand) younger than 12 years quadriplegia, and temporary loss of vision) after first dose; may Possible respiratory depression when combined with benzodiazepines, barbiturates, codeine require hospitalization or its derivatives, or other muscle relaxants Allergy-type reactions may occur after the first to fourth dose; Contraindicated in acute intermittent porphyria may be mild (e.g., cutaneous rash) or more severe (e.g., asthma FDA pregnancy category C attack, angioneurotic edema, hypotension, or anaphylactic shock); antihistamines, epinephrine, or corticosteroids may be needed Chlorzoxazone Adults: 250 to 750 mg three to four Dizziness, drowsiness Avoid use in patients with hepatic impairment 15 to 77 (generic) (Parafon Forte)2 times daily Red or orange urine Possible respiratory depression when combined with benzodiazepines, barbiturates, codeine 180 (brand) Children: 125 to 500 mg three to four GI irritation and rare GI bleeding or its derivatives, or other muscle relaxants times daily; or 20 mg per kg daily in Hepatoxicity (rare); discontinue with elevated liver function test FDA pregnancy category C three or four divided doses Cyclobenzaprine 5 mg three times daily; may increase Anticholinergic effect (drowsiness, dry mouth, urinary retention, Most studied skeletal muscle relaxant 120 to 140 (generic) (Flexeril)3 to 10 mg three times daily increased intraocular pressure) Long elimination half-life 157 (brand) Rare but serious adverse effects are arrhythmias, seizures, 5-mg dose as effective as 10-mg, with fewer adverse effects myocardial infarction Avoid in older patients and in patients with glaucoma Possible drug interaction with CYP450 inhibitors Seizures reported with concomitant use of tramadol (Ultram); combination should be avoided in patients with medical conditions that may induce seizures Contraindicated in patients with arrhythmias, recent myocardial infarction, or congestive heart failure FDA pregnancy category B Diazepam Adults: 2 to 10 mg three to four times Dizziness, drowsiness, confusion Also an antispastic agent 11 to 23 (generic) (Valium)4 daily Abuse potential Long elimination half-life; avoid in older patients and in patients with hepatic impairment 184 (brand) Children: 0.12 to 0.80 mg per kg daily Possible drug interaction with CYP450 inhibitors in three or four divided doses Complete blood count and liver function tests indicated for prolonged use FDA pregnancy category D; avoid especially in the first trimester Metaxalone 800 mg three to four times daily Drowsiness, dizziness, headache, nervousness Use with caution in patients with liver failure 275; generic not available (Skelaxin)5 Not recommended in children younger Leukopenia or hemolytic anemia (rare) Possible respiratory depression when combined with benzodiazepines, barbiturates, codeine than 12 years Liver function test elevation (rare) or its derivatives, or other muscle relaxants Nausea, vomiting, and diarrhea (rare) Less dizziness and drowsiness than other skeletal muscle relaxants Paradoxical muscle cramps FDA pregnancy category C Methocarbamol 1,500 mg four times daily for first two Black, brown, or green urine possible Possible respiratory depression when combined with benzodiazepines, barbiturates, codeine 15 to 58 (generic) (Robaxin)6 to three days, followed by 750 mg Mental status impairment or its derivatives, or other muscle relaxants 176 (brand) four times daily Possible exacerbation of myasthenia gravis symptoms FDA pregnancy category C; reports of fetal abnormalities Orphenadrine 100 mg twice daily Anticholinergic effect (drowsiness, dry mouth, urinary retention, Long elimination half-life 110 to 140 (generic) (Norflex)7 Combination products are dosed three increased intraocular pressure) Reduced dosages in older patients 162 (brand) to four times daily Aplastic anemia (rare) Avoid in patients with glaucoma, cardiospasm, or myasthenia gravis GI irritation Decreases effect of phenothiazines (e.g., chlorpromazine [Thorazine†], promethazine [Phenergan]) Confusion, tachycardia, hypersensitivity reaction (with high doses) FDA pregnancy category C Tizanidine 4 mg initially; may increase by 2 to Dose-related hypotension, sedation, and dry mouth Also antispastic agent 329 (generic) (Zanaflex)8,9 4 mg every six to eight hours until Hepatotoxicity; monitor liver function tests at baseline and one, Do not use with CYP1A2 inhibitors, ciprofloxacin (Cipro) or fluvoxamine (Luvox CR) 437 (brand) relief three, and six months Caution with CYP1A2 inhibitors, central nervous system depressants, or alcohol Do not exceed 36 mg daily Withdrawal and rebound hypertension may occur in patients Decreased effectiveness with oral contraceptives discontinuing therapy after receiving high doses for long period FDA pregnancy category C of time; tapering is recommended NOTE: The table contains only selected highlights about these medications. All of these drugs may
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